4x50: Difference between revisions
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The | ==Crystal structure of FimH in complex with biphenyl alpha-D-mannopyranoside== | ||
<StructureSection load='4x50' size='340' side='right'caption='[[4x50]], [[Resolution|resolution]] 2.00Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4x50]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4X50 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4X50 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3X8:BIPHENYL-4-YL+ALPHA-D-MANNOPYRANOSIDE'>3X8</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4x50 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x50 OCA], [https://pdbe.org/4x50 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4x50 RCSB], [https://www.ebi.ac.uk/pdbsum/4x50 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4x50 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/FIMH_ECOLI FIMH_ECOLI] Involved in regulation of length and mediation of adhesion of type 1 fimbriae (but not necessary for the production of fimbriae). Adhesin responsible for the binding to D-mannose. It is laterally positioned at intervals in the structure of the type 1 fimbriae. In order to integrate FimH in the fimbriae FimF and FimG are needed. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Urinary tract infections caused by uropathogenic E. coli are among the most prevalent infectious diseases. The mannose-specific lectin FimH mediates the adhesion of the bacteria to the urothelium, thus enabling host cell invasion and recurrent infections. An attractive alternative to antibiotic treatment is the development of FimH antagonists that mimic the physiological ligand. A large variety of candidate drugs have been developed and characterized by means of in vitro studies and animal models. Here we present the X-ray co-crystal structures of FimH with members of four antagonist classes. In three of these cases no structural data had previously been available. We used NMR spectroscopy to characterize FimH-antagonist interactions further by chemical shift perturbation. The analysis allowed a clear determination of the conformation of the tyrosine gate motif that is crucial for the interaction with aglycone moieties and was not obvious from X-ray structural data alone. Finally, ITC experiments provided insight into the thermodynamics of antagonist binding. In conjunction with the structural information from X-ray and NMR experiments the results provide a mechanism for the often-observed enthalpy-entropy compensation of FimH antagonists that plays a role in fine-tuning of the interaction. | |||
The Tyrosine Gate of the Bacterial Lectin FimH: A Conformational Analysis by NMR Spectroscopy and X-ray Crystallography.,Fiege B, Rabbani S, Preston RC, Jakob RP, Zihlmann P, Schwardt O, Jiang X, Maier T, Ernst B Chembiochem. 2015 May 26;16(8):1235-46. doi: 10.1002/cbic.201402714. Epub 2015, May 4. PMID:25940742<ref>PMID:25940742</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4x50" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Adhesin 3D structures|Adhesin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Escherichia coli K-12]] | |||
[[Category: Large Structures]] | |||
[[Category: Ernst B]] | |||
[[Category: Fiege B]] | |||
[[Category: Jakob RP]] | |||
[[Category: Jiang X]] | |||
[[Category: Maier T]] | |||
[[Category: Preston RC]] | |||
[[Category: Rabbani S]] | |||
[[Category: Schwardt O]] | |||
[[Category: Zihlmann P]] | |||
Latest revision as of 13:47, 10 January 2024
Crystal structure of FimH in complex with biphenyl alpha-D-mannopyranosideCrystal structure of FimH in complex with biphenyl alpha-D-mannopyranoside
Structural highlights
FunctionFIMH_ECOLI Involved in regulation of length and mediation of adhesion of type 1 fimbriae (but not necessary for the production of fimbriae). Adhesin responsible for the binding to D-mannose. It is laterally positioned at intervals in the structure of the type 1 fimbriae. In order to integrate FimH in the fimbriae FimF and FimG are needed. Publication Abstract from PubMedUrinary tract infections caused by uropathogenic E. coli are among the most prevalent infectious diseases. The mannose-specific lectin FimH mediates the adhesion of the bacteria to the urothelium, thus enabling host cell invasion and recurrent infections. An attractive alternative to antibiotic treatment is the development of FimH antagonists that mimic the physiological ligand. A large variety of candidate drugs have been developed and characterized by means of in vitro studies and animal models. Here we present the X-ray co-crystal structures of FimH with members of four antagonist classes. In three of these cases no structural data had previously been available. We used NMR spectroscopy to characterize FimH-antagonist interactions further by chemical shift perturbation. The analysis allowed a clear determination of the conformation of the tyrosine gate motif that is crucial for the interaction with aglycone moieties and was not obvious from X-ray structural data alone. Finally, ITC experiments provided insight into the thermodynamics of antagonist binding. In conjunction with the structural information from X-ray and NMR experiments the results provide a mechanism for the often-observed enthalpy-entropy compensation of FimH antagonists that plays a role in fine-tuning of the interaction. The Tyrosine Gate of the Bacterial Lectin FimH: A Conformational Analysis by NMR Spectroscopy and X-ray Crystallography.,Fiege B, Rabbani S, Preston RC, Jakob RP, Zihlmann P, Schwardt O, Jiang X, Maier T, Ernst B Chembiochem. 2015 May 26;16(8):1235-46. doi: 10.1002/cbic.201402714. Epub 2015, May 4. PMID:25940742[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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